Chronic pain associated with temporomandibular joint (TMJ) disorders is a major problem in the United States, with poorly defined pathophysiological mechanisms. It is the long-term objective of this application to develop a novel in vivo model of painful mechanically-induced TMJ osteoarthritis in the rat and utilize this model to define mechanisms of glial reactivity and cytokine expression that contribute to TMJ pain. In this proposed research plan, we will integrate bioengineering approaches, behavioral test instruments and biochemical assays to define mechanisms of painful osteoarthritis (OA) in the TMJ. We have preliminary data supporting steady mouth-opening as producing sustained mechanical allodynia in the rat. In this proposal we extend those studies to define the pathogenesis of persistent behavioral sensitivity associated with the development of cartilage degeneration in the TMJ. The goals of the proposed research project are to develop a novel pain model of osteoarthritis in the TMJ via non-invasive and non-adjuvant methods, and to utilize this model to understand the relationship between osteoarthritic changes, behavioral sensitivity, and glial activation in the CMS. We hypothesize that a repeated mouth-opening protocol can induce permanent osteoarthritic changes in TMJ cartilage that depend on loading frequency and applied force. Further, such changes in TMJ cartilage give rise to elevated glial pro-inflammatory cytokine expression in the CNS which contribute to the initiation and maintenance of sustained allodynia, mimicking persistent orofacial pain symptoms. The specific aims of this research are to: (1) develop an in vivo rat model of repeated mouth-opening which produces TMJ osteoarthritic lesions and persistent behavioral sensitivity; and (2) utilize immunophenotyping and cell sorting techniques to separate glial and neuronal cell populations, and real-time PCR to probe cytokine expression profiles in those cells during the onset and maintenance of chronic behavioral sensitivity. Findings from this developmental research project will establish a novel rat model for defining the etiology of TMJ pain and potential future treatment strategies. Relevance: The incidence of TMJ osteoarthritis continues to rise due to the aging United States population. This places growing strain on the United States healthcare system, making it difficult to achieve the objective of 'Healthy People 2010.' This research proposal lays the foundation for defining the cellular mechanisms in the joint and central nervous system associated with chronic pain in the TMJ. It also identifies the time course of physiologic mechanisms of these disorders, and will provide the basis for future studies to investigate potential pharmacologic therapies for chronic TMJ pain. [unreadable] [unreadable] [unreadable]